Spinal hierachy and noxious cardiac sensory processing

描述（由申请人提供）：本项目的目的是评价心脏相关迷走神经和交感神经感觉输入如何影响上颈（C1-C2）和上胸（T3-T4）脊髓神经元，以最终改变心脏的传出神经元输出。这一建议是基于最近的观察，C1-C2神经元调节腰骶神经元对骨盆输入的反应，迷走神经感觉信息兴奋C1-C2神经元，以及心脏交感神经输入胸段上升通过propriospinal通路影响C1-C2神经元。我们假设，在神经控制的层次结构，调节心脏功能，C1-C2脊髓神经元的影响上胸神经元的心脏感觉信息的处理，从而确定自主外流到心脏。神经生理学实验旨在确定化学或缺血性心脏应激在C1-C2和T3-T4神经元中产生的迷走神经和交感神经传入输入的处理，并确定上颈神经元处理对T3-T4神经元的影响。神经解剖学实验（测量c-Fos表达和上颈段脊髓本体通路的束追踪）旨在确定心脏应激期间的神经元激活，并为脊髓本体解剖组织提供证据。每个特定目标的微透析实验将测量基础状态和心脏应激期间心室心肌间质液中的去甲肾上腺素和肾上腺素水平。心包内注射致痛化学物质或冠状动脉闭塞将产生心脏应激。具体目标包括：1）双侧迷走神经切断前后和激活T3-T4节段GABAB受体前后，C1-C2下行脊髓本体神经元的心脏感觉加工和C1-C2和T3-T4节段c-Fos的表达; 2）破坏或刺激C1-C2节段细胞体对T3-T4神经元的影响，以及c-Fos表达的测量; 3）急性心肌缺血的影响; 4）短时间背索激动对心脏信息处理的影响。这些研究将为确定C1-C2神经元对心脏控制层次的影响提供基础。

DESCRIPTION (provided by applicant): The purpose of this project is to evaluate how cardiac-related vagal and sympathetic sensory inputs influence upper cervical (C1-C2) and upper thoracic (T3-T4) spinal neurons to ultimately modify efferent neuronal output to the heart. This proposal is based on recent observations that C1-C2 neurons modulate responses of lumbosacral neurons to pelvic inputs, that vagal sensory information excites C1-C2 neurons, and that cardiac sympathetic input to thoracic segments ascends via propriospinal pathways to influence C1-C2 neurons. We hypothesize that, within the hierarchy of neural control that regulates cardiac function, neurons in C1-C2 spinal cord influence the processing of cardiac sensory information in upper thoracic neurons, and thereby determine autonomic outflow to the heart. Neurophysiological experiments are designed to determine the processing of vagal and sympathetic afferent inputs produced by chemical or ischemic cardiac stress in C1-C2 and T3-T4 neurons, and to determine the influence of upper cervical neuronal processing on T3-T4 neurons. Neuroanatomical experiments (measurement of c-Fos expression and tract tracing of propriospinal pathways from upper cervical segments) are designed to determine neuronal activation during cardiac stress and to provide evidence for propriospinal anatomical organization. Microdialysis experiments in each specific aim will measure norepinephrine and epinephrine levels in the interstitial fluid of the ventricular myocardium in the basal state and during cardiac stress. Cardiac stress will be produced by intrapericardial injection of algogenic chemicals or by coronary artery occlusion. Specific aims will address 1) cardiac sensory processing in C1-C2 descending propriospinal neurons and c-Fos expression in C1-C2 and T3-T4 segments before and after bilateral vagotomy and before and after activating GABAB receptors in T3-T4 segments; 2) effects of disrupting or stimulating cell bodies in C1-C2 segments on T3-T4 neurons, and measurements of c-Fos expression; 3) effects of acute myocardial ischemia; 4) effects of short-term dorsal cord activation on cardiac information processing. These studies will provide a basis for determining the impact of C1-C2 neurons on the hierarchy of cardiac control.